A sage expression, you make the road by walking, captures the nature of accompaniment in partnership development. The purpose of this action research project was to examine the partnership of a city school and an urban university as one that engaged mutual generation of knowledge from all participants. Action research, where participants are co-equals in decision-making, enhances the co-construction of knowledge and applied practice when stakeholders work to achieve more practical goals. Two high school co-instructors and a university faculty member examined what initially brought them together – a classroom instructional need. While designing and implementing an investigation of the use of class instructional time, they simultaneously conducted a self-study action research project about the dynamics of their partnership and how to improve it. Critical interviews revealed challenges to integrating research findings into practice as well as convergent benefits of partnership development that may be relevant to partnerships of all kinds.
Key Terms: Action research, collaboration, collaborative organizations, mode 2 knowledge creation, partnership development, research-practice gap
One proactive approach to increasing student engagement in schools is implementing Positive Behavior Intervention and Support (PBIS) strategies. PBIS focuses on prevention and concentrates on quality-of-life issues that include improved academic
achievement, enhanced social competence, and safe learning and teaching environments. This study is a replication of a study that investigated the combination of active supervision, precorrection, and explicit timing. The purpose of the study was to decrease student problem behavior, reduce transition time, and support maintenance of the intervention in the setting. Results show that active supervision, precorrection, and explicit timing decreased student problem behavior, decreased the duration of transitions in two instructional periods, and the intervention was maintained in the setting. Implications, limitations, and future research are discussed.
Keywords: active supervision, explicit timing, Positive Behavior Intervention and Support, precorrection, urban education
The purpose of this study was to define and examine the IASB’s
governance network. The IASB’s governance network was bound to include 14
organisational members and 407 individual actors. I used social network
methodology to examine the professional and geographic perspectives
represented as well as the extent to which the governance network was
structurally embedded. It was found that the network forms a definable
hierarchy that exhibits qualities of structural embeddedness. Banking interests
were more embedded within the governance network than any other
professional, academic, or social group. Also, a strong Western influence was
detected. The societal benefit of this effort was to engage society in general and
accounting researchers in particular in hopes of encouraging discourse about
regulatory processes with both macro and micro consequences.
There is good news for those who desire to live in stable racially integrated neighborhoods in Hamilton County. Starting with the 1970 Census, racial segregation declined modestly in the City of Cincinnati and to a smaller extent in suburban areas of the county. This occurred as, over the three decades from 1970 to 2000, an increasing number of communities found blacks and whites living together on the same blocks. Indeed, at the 2000 Census, about one-quarter of Hamilton County communities were racially integrated by the measures used in this study. Moreover, starting with the 1980 Census, fourteen of those communities have maintained stable racial integration. This is in sharp contrast to the results of a 1984 study that found few racially integrated neighborhoods between 1940 and 1980, and that those that did exist generally did so only as neighborhoods changed from largely white to largely black. This news is also in sharp contrast to newspaper accounts of the 2000 Census that reported that “Cincinnati” remained one of the most racially segregated cities in the country. However, many of these reports confused the City of Cincinnati with the much larger Cincinnati Primary Statistical Metropolitan Area, which ranked the 8th or 9th most segregated metropolitan area in the country depending on the study. In actuality, the City of Cincinnati ranked 67th most segregated among 245 cities with populations over 100,000.
Lloyd C. Engelbrecht (born 1927) is Professor Emeritus of Art History at the University of Cincinnati. He is author of Moholy-Nagy: Mentor to Modernism (Cincinnati: Flying Trapeze Press, 2009), two volumes. Moholy-Nagy: Mentor to Modernism is the first comprehensive, fully documented biography of the most fully-rounded creative figure of the twentieth century.
This introductory essay was originally published in German in 2014 in the Beiheft, or supplementary volume, that accompanies the first German edition of Vision in Motion.
László Moholy-Nagy, Sehen in Bewegung, Deutsche Fassung von László Moholy-Nagys vision in motion in der Übersetzung von Herwig Engelmann [on verso of title page: “Mit einem Beiheft mit Texten von Lloyd C. Engelbrecht, Hattula Moholy-Nagy und Philipp Oswalt”]
(Leipzig: Spector Books, 2014)
László Moholy-Nagy, Vision in Motion, “id BOOK, INSTITUTE OF DESIGN” (Chicago: Paul Theobald, 1947)
Lloyd C. Engelbrecht (born 1927) is Professor Emeritus of Art History at the University of Cincinnati. He is author of Moholy-Nagy: Mentor to Modernism (Cincinnati: Flying Trapeze Press, 2009). He will supply addenda and corrigenda for this book on a continuing basis.
In urban middle schools, educators find it challenging to meet the literacy needs of the many struggling readers in their classrooms, including language-minority (LM) learners and students from low-income backgrounds. One strategy for improving these students' reading comprehension is to teach essential academic vocabulary in a meaningful, engaging, and systematic way. This article describes the development and evaluation of an academic vocabulary curriculum for sixth-grade mainstream classrooms with large numbers of LM learners who struggle with comprehension. In a study conducted in 21 sixth-grade classrooms, the curriculum was found to be effective both in improving students' vocabulary and reading comprehension and in supporting teachers' learning about how to teach academic vocabulary. Seven universal learnings for all classrooms are described and illustrated with specific examples of activities, perspectives from teachers, and insights from students, drawn from the study.
The present study aims to advance the extant research base by evaluating the implementation and effectiveness of an academic vocabulary program designed for use in mainstream middle school classrooms with high proportions of language minority learners. The quasi-experimental, mixed-methods study was conducted in 21 classes (13 treatment matched to 8 control) in seven middle schools in a large district, with 476 sixth-grade students (346 language minority learners, 130 native English speakers). Classroom observations and teacher logs indicated the 18-week program was implemented with good fidelity and that the approach contrasted sharply with the standard district English language arts (ELA) curriculum. Multilevel modeling indicated that the program resulted in significant effects on several aspects of vocabulary knowledge, including meanings of taught words (d = 0.39; p < .0001), morphological awareness (d = 0.20; p = .0003), and the word meanings as presented in expository text (d = 0.20; p = .0227). The program also yielded marginally significant, but promising effects on a depth of word knowledge measure (d = 0.15; p =0.0830) and a norm-referenced measure of reading comprehension (d = 0.15; p = .0568). No effects were found on a norm-referenced vocabulary measure. These effects were comparable for language minority learners and their native-English-speaking classmates. Data from teachers shed light on the challenges of meeting students' diverse instructional needs and the roles of curriculum and professional networks in building instructional capacity. The findings show promise in developing effective multifaceted vocabulary instruction for implementation by ELA teachers in middle school classrooms with high numbers of language minority learners.
The alternative education field lacks a common definition and has a major divide between the differing philosophies of alternative programs; little empirical evidence is available to identify the components necessary to create effective alternative educational programs. Tremendous growth in the availability of alternative programs in the United States over the past several decades, however, illustrates continuing demand for such programs as well as the need for research on the characteristics that constitute effective alternative programs. In this article, the authors study exemplary alternative programs in 3 racially and economically diverse communities to characterize the school climate as viewed by the students and the staff. At this relatively early stage in the field of alternative education, it is essential to examine the similarities, as well as any differences, in the social climate of highly effective alternative programs and to consider their potential relationship with student academic and behavioral success. Furthermore, it is important to recognize how these findings might be one foundation for future inquiry and research on alternative education. [PUBLICATION ABSTRACT]
Martin Buber is one of the luminaries of modern Jewish thought, and yet prior to 1944 his work was little known in the Anglophone world as few of his books had been translated into English. In 1933, Buber asked Adolph Oko, the Librarian of the Hebrew Union College (H.U.C.) in Cincinnati, Ohio to help him find a publishers for his work. The correspondence about securing a publisher between Buber and Oko eventually expanded to include the theologian Abraham Joshua Heschel (then teaching at H.U.C.) and the historian Hans Kohn, a former student of Buber who was now a refugee teaching in the U.S.
Throughout much of his career the Anglo-Jewish historian Cecil Roth visited the U.S. and lectured to American Jewish students. Indeed, his first academic appointment was as a visiting professor at the Jewish Institute in Religion in New York City, and he was a regular teacher at the summer institutes of the Intercollegiate Menorah Society. Yet, he only wrote one short article (in 1963) that focused exclusively on American Jewish history, which was commissioned by Jacob Rader Marcus, the “Dean of American Jewish Historians.” An examination of Roth’s correspondence over a thirty plus year period reveals that his discussions of the nature and purpose of Jewish history was largely shaped by his relationship with American Jewry.
After the liberation of North Africa, in 1943, it was discovered by policy makers within the Grand Alliance that both the British and Americans were in the process of making documentary films about the Operation Torch campaign. Fearful that separate films would highlight potential dissension with the Anglo-American alliance, the director Frank Capra was dispatched to London to coordinate his U.S. Army documentary with his British counter-parts. Instead of a smooth process, the joint film project bogged down in inter-service and inter-allied rivalry’s that delayed the completion of Tunisian Victory for over a year.
Remembered today as one of the great popularizers of Jewish history, in the inter-war year the Anglo-Jewish historian Cecil Roth was unable to secure an academic appointment until 1939. As such he turned to writing popular history as a means of support, and while some academic historians discounted his work (then and now), an examination of Roth’s correspondence with individuals such Henry Hurwitz of the Intercollegiate Menorah Society, reveal that Roth worked assiduously to develop an approach to history that would be both academically sound and “useful” to those readers who wanted to understand the contours of Jewish life.
In an effort to promote an image of Allied unity on the eve of Operation Overlord, the Allied invasion of Western Europe, a Joint Anglo-American Film Commission was established with the goal of making a series of short documentaries on the liberation of the continent. Unfortunately, despite the prior planning, the plans for a series of joint films fell victim to competing ideologies about how to showcase the allied campaign. In an effort to salvage the situation the American film maker George Stevens was brought in to make a single long documentary, highlighting the campaign from D-Day to VE-Day. The resulting film, The True Glory, won an Oscar for best documentary of 1945, but in fact was the result of a failure of Allied film propaganda policy.
The foreground Veil of material that lies in front of the Orion Nebula is the best studied sample of the interstellar medium because we know where it is located, how it is illuminated, and the balance of thermal and magnetic energy. In this work, we present high-resolution STIS observations toward the Trapezium, with the goal of better understanding the chemistry and geometry of the two primary Veil layers, along with ionized gas along the line of sight. The most complete characterization of the rotational/vibrational column densities of H2 in the almost purely atomic components of the Veil are presented, including updates to the Cloudy model for H2 formation on grain surfaces. The observed H2 is found to correlate almost exclusively with Component B. The observed H2, observations of CI, CI*, and CI**, and theoretical calculations using Cloudy allow us to place the tightest constraints yet on the distance, density, temperature, and other physical characteristics for each cloud component. We ﬁnd the H2 excitation spectrum observed in the Veil is incompatible with a recent study that argued that the Veil was quite close to the Trapezium. The nature of a layer of ionized gas lying between the Veil and the Trapezium is characterized through the emission and absorption lines it produces, which we ﬁnd to be the blueshifted component observed in S III and P III absorption. We deduce that, within the next 30–60 thousand years, the blueshifted ionized layer and Component B will merge, which will subsequently merge with Component A in the next one million years.
Science teachers are often charged with providing discipline-specific literacy instruction. However, little is known about the reading and writing genres, or text types, typically found in these classrooms. In particular, there is a lack of knowledge about what opportunities adolescents have to engage with the genres privileged in science to learn the discipline's specialized ways of making meaning and communicating knowledge. This article reports on a case study of the reading and writing genres found within four middle-grade science classrooms in one small all-female school. Results suggest that although a variety of text genres were present, there was little discussion of how and why science content was presented in particular ways. Notably, students also had far more opportunities to read than write extended nonfiction. Teachers can cultivate a more reciprocal relation between reading and writing in science by using genres that students read as models for their writing.
Cincinnati's struggle for fair housing has been a long and often contested one. A handful of neighborhoods in the Queen City and its metropolitan area are now stably racially integrated and more seem likely to join that number in the near future. Yet there is much more work to be done, as the metropolitan area as a whole remains one of the most segregated in the nation.
Several constitutive theories have been proposed in the literature to model the viscoelastic response of soft tissue, including widely used rheological constitutive models. These models are characterized by certain parameters (“time constants”) that define the time scales over which the tissue relaxes. These parameters are primarily obtained from stress relaxation experiments using curve-fitting techniques. However, the question of how best to estimate these time constants remains open.
As a step towards answering this question, we develop an optimal experimental design approach based on ideas from information geometry, namely Fisher information and Kullback-Leibler divergence. Tissue is modeled as a standard linear solid and described using a one- or two-term Prony series. Treating the time constants as unknowns, we develop expressions for the Fisher information and Kullback-Leibler divergence that allow us to maximize information gain from experimental data. Based on the results of this study, we propose that the largest time constant estimated from a stress relaxation experiment for a linear viscoelastic material should be at most one-fifth of the total time of the experiment in order to maximize information gain.
The study of the propagation of multiple cracks is essential to modeling and predicting structural integrity. The interaction between two cracks depends on a number of factors such as the domain geometry, the relative crack sizes and the separation between the two crack tips. In this paper, we study the interaction between two dynamically propagating cracks. We use the phase field method to track the crack paths, since this method can handle complex crack behavior such as crack branching, without any ad hoc criteria for crack evolution. The results from our dynamic simulations indicate that, unlike crack inter- action under quasi-static or fatigue loading, the presence of another crack does not accelerate crack propagation when dynamic loads are applied. However, some similarities in the crack topologies are observed for both quasi-static and dynamic loading.
Lloyd C. Engelbrecht (born 1927) is Professor Emeritus of Art History at the University of Cincinnati. In collaboration with his late wife, June-Marie F. Engelbrecht (1930-2009), he has been researching, writing about and speaking about architect and designer Henry C. Trost (1860-1933) and his family firm of Trost & Trost.
On May 8, 2014, Lloyd Engelbrecht was invited to speak at the University of Texas at El Paso as part of a Trost symposium. The following is an excerpt from the official announcement of the symposium:
In celebration of Trost’s architectural legacy, UTEP Special Collections will host the “Trost Lecture Series” at 6 p.m. May 8  in the UTEP Library, Blumberg Auditorium, room 111.
The event will feature speakers Dr. Troy Ainsworth, executive director of El Camino Real de Tierra Adentro Trail Association (CARTA); Joe and Lanna Duncan, owners of the Trost-designed El Capitan Hotel in Van Horn, Texas and El Paisano Hotel in Marfa, Texas; and Dr. Lloyd Engelbrecht, co-author of Henry C. Trost: Architect of the Southwest.
A public exhibit featuring family photos, sketches, blueprints and photographs of the buildings Trost designed in El Paso and throughout the Southwest will be on display May 10 in the UTEP Library’s atrium on the third floor.
The lecture and exhibit were part of Trost Week, May 3-10, 2014, which was organized by the Texas Trost Society, a new nonprofit group that advocates for the preservation of Trost & Trost architecture.
Hyperelastic constitutive models of soft tissue mechanical behavior are extensively used in applications like computer-aided surgery, injury modeling, etc. While numerous constitutive models have been proposed in the literature, an objective method is needed to select a parsimonious model that represents the experimental data well and has good predictive capability. This is an important problem given the large variability in the data inherent to soft tissue mechanical testing.
In this work, we discuss a Bayesian approach to this problem based on Bayes factors. We propose a holistic framework for model selection, wherein we consider four different factors to reliably choose a parsimonious model from the candidate set of models. These are the qualitative fit of the model to the experimental data, evidence values, maximum likelihood values, and the landscape of the likelihood function. We consider three hyperelastic constitutive models that are widely used in soft tissue mechanics: Mooney-Rivlin, Ogden and exponential. Three sets of mechanical testing data from the literature for agarose hydrogel, bovine liver tissue, porcine brain tissue are used to calculate the model selection statistics. A nested sampling approach is used to evaluate the evidence integrals. In our results, we highlight the robustness of the proposed Bayesian approach to model selection compared to the likelihood ratio, and discuss the use of the four factors to draw a complete picture of the model selection problem.
Members of the fungal genus Pneumocystis colonize healthy mammalian hosts
without causing apparent disease, but colonization in immunocompromised hosts
may result in a potentially fatal pneumonia known as Pneumocystis pneumonia.
Although Pneumocystis are fungi, this genus has characteristics that make it atypical
among other fungi. Pneumocystis do not appear to synthesize the major fungal sterol,
ergosterol, and biochemical analyses have shown that they utilize cholesterol rather
than ergosterol as the bulk sterol. Pneumocystis carinii appears to scavenge exogenous sterols, including cholesterol, from its mammalian host. As a result, it has long been held that their ability to scavenge cholesterol from their hosts, and their inability to undergo sterol biosynthesis, makes them resistant to antifungal drugs that target ergosterol or ergosterol biosynthesis. However, genome scans and in vitro assays indicate the presence of sterol biosynthetic genes within the P. carinii genome, and targeted inhibition of these enzymes resulted in reduced viability of P. carinii,
suggesting that these enzymes are functional within the organism. Heterologous
expression of P. carinii sterol genes, along with biochemical analyses of the lipid
content of P. carinii cellular membranes, have provided an insight into sterol
biosynthesis and the sterol-scavenging mechanisms used by these fungi.
Organisms in the genus Pneumocystis are ubiquitous, opportunistic pathogenic fungi capable of causing a
lethal pneumonia in immunocompromised mammalian hosts. Pneumocystis spp. are unique members of the
fungal kingdom due to the absence of ergosterol in their cellular membranes. Although these organisms were
thought to obtain cholesterol by scavenging, transcriptional analyses indicate that Pneumocystis carinii encodes
gene homologs involved in sterol biosynthesis. To better understand the sterol pathway in these uncultivable
fungi, yeast deletion strains were used to interrogate the function and localization of P. carinii lanosterol synthase (ERG7). The expression of PcErg7p in an ERG7-null mutant of the yeast Saccharomyces cerevisiae did not alter its growth rate and produced a functional lanosterol synthase, as evidenced by the presence of
lanosterol detected by gas chromatographic analysis in levels comparable to that produced by the yeast enzyme. Western blotting and fluorescence microscopy revealed that, like the S. cerevisiae Erg7p, the PcErg7p localized to lipid particles in yeast. Using fluorescence microscopy, we show for the first time the presence of apparent lipid particles in P. carinii and the localization of PcErg7p to lipid particles in P. carinii. The detection of lipid particles in P. carinii and their association with PcErg7p therein provide strong evidence that the enzyme serves a similar function in P. carinii. Moreover, the yeast heterologous system should be a useful tool for further analysis of the P. carinii sterol pathway.
The previous study for which this one serves as an update concluded that there was good news for those who wished to live in racially integrated communities in Hamilton
County. The news remains good. At the 2010 census, fifty-four suburban Hamilton
County communities and Cincinnati neighborhoods, over one-third of the total,
containing 45% of the total population of the county, were at least modestly racially
integrated (Table 9).2 This continues trends that began as early as 1970 when seven
communities achieved integration that persisted for at least forty years. At the 1980
census, twelve achieved racial integration that lasted for at least thirty years. And at the 1990 census, ten became integrated with that persisting for at least the next twenty years. Together, twenty-nine communities have remained racially integrated for at least twenty years.
At the same time, the dissimilarity index (DI), a standard measure of residential
integration, showed improved black/white integration for both the city of Cincinnati and
Hamilton County as a whole (Table 1). Cincinnati’s DI dropped from 91.2 in 1950, its
highest point, to 64.8 in 2010. Hamilton County’s DI dropped from 82.8 in 1980, the
earliest for which we have data, to 71.3 in 2010. This means that increasing numbers of whites and blacks are living on the same blocks in a number of communities here.
The desirability of these integrated neighborhoods has apparently remained steady over time. Although both the city and the county have lost population, the integrated
neighborhoods have proportionally lost no greater population than the rest. Moreover, in the last decade, conventional wisdom to the contrary, several of the long-term integrated communities experienced increases in the white percentage of their population.
When we looked at socio-economic conditions throughout the county as measured by
seven indicators drawn from the census, we found a range of values for the integrated
communities. Some are clearly in quite good shape and improving and some show signs of decay. On a scale that aggregates five of these indicators, integrated communities on the average fell between the values for the city of Cincinnati as a whole and for suburban Hamilton County. This is particularly good news as the declining economy has certainly hurt the African Americans population more than the rest of the population. Because of this, the integrated communities might be expected to show a greater decline than the rest of the county, and while some of them have been hurt, on the average, they seem to be holding their own in comparison to the rest of the county.
Finally, the city of Cincinnati, which has long seen an increase in black population and a decrease in white population, in the 2000s saw a significant slow-down in the decline of white population and an actual decrease in black population. This suggests that the black/white ratio may stabilize in the city in the near future.
In the spring of 2001 the hilly uplands immediately northwest of the modern city of Durres were for the first time investigated using the techniques of intensive surface survey. In total, an area of six square kilometers was explored and twenty-nine sites were defined, most of them new. Remains of Greek antiquity were plentiful and include unpublished inscriptions and graves. One site may be the location of a previously unknown Archaic temple. Included in this article are descriptions of the areas investigated, a list of sites, and a catalogue of the most diagnostic artifacts recovered. Patterns of settlement and land use are discussed and compared to those recorded by other surveys in Albania.
Lloyd C. Engelbrecht (born 1927) is Professor Emeritus of Art History at the University of Cincinnati. His article, “Wood, Plywood and Veneer, Cranbrook, the New Bauhaus and the W. P. A.: the Origins of the Eames Chair of 1946,” had its origins in a paper presented at a symposium, “Bauhaus, New Bauhaus, W. P. A.: Chairs for Mid-Century,” October 17, 1981, at the Mid-America Conference of the College Art Association, meeting in Milwaukee. The article was expanded and eventually completed in 1987, but it was never published. The author asked that his late wife, June-Marie F. Engelbrecht (1930-2009), be given credit for her immense amount of help with the research and writing of the article.
Lloyd C. Engelbrecht (born 1927) is Professor Emeritus of Art History at the University of Cincinnati. This study guide was used to illustrate some of his classroom presentations and also on-site visits with his students to Prairie School buildings. This version of the study guide dates from May 10, 1994.
The archival profession has long attempted to define what constitutes a professional archivist. These debates over education, training, and certification have lasted decades, however few studies have been completed on how the employment market for archivists has changed in response to these professional challenges. This study looks at almost a thousand professional archivist job advertisements between late 2006 and early 2014 to understand the current prevailing recruitment criteria. It is broader in scope and time period than other recent studies. Overall, the market was determined to be mostly stable during the study period.
The problem of assigning a group of Unmanned Aerial Vehicles (UAVs) to perform spatially distributed tasks often requires that the tasks will be performed as quickly as possible. This problem can be defined as the Min–Max Multiple Depots Vehicle Routing Problem (MMMDVRP), which is a benchmark combinatorial optimization problem. In this problem, UAVs are assigned to service tasks so that each task is serviced once and the goal is to minimize the longest tour performed by any UAV in its motion from its initial location (depot) to the tasks and back to the depot. This problem arises in many time-critical applications, e.g. mobile targets assigned to UAVs in a military context, wildfire fighting, and disaster relief efforts in civilian applications. In this work, we formulate the problem using Mixed Integer Linear Programming (MILP) and Binary Programming and show the scalability limitation of these formulations. To improve scalability, we propose a hierarchical market-based solution (MBS). Simulation results demonstrate the ability of the MBS to solve large scale problems and obtain better costs compared with other known heuristic solution.
Unmanned Air Vehicle (UAV) teams are anticipated to provide surveillance support through algorithms, software, and automation. It is desirable to have algorithms that compute effective and efficient routes for multiple UAVs across a variety of missions. These algorithms must be realizable, practical, and account for uncertainties. In surveillance missions, UAVs act as mobile wireless communication nodes in a larger, underlying network consisting of targets where information is to be collected and base stations where information is to be delivered. The role of UAVs in these networks has primarily been to maintain or improve connectivity while undervaluing routing efficiency. Moreover, many current routing strategies for UAVs ignore communication constraints even though neglecting communication can lead to suboptimal tour designs. Generating algorithms for autonomous vehicles that work effectively despite these communication restrictions is key for the future of UAV surveillance missions. A solution is offered here based on a variation of the traditional vehicle routing problem and a simple communication model. In this work, the new routing formulation is defined, analyzed, and a heuristic approach is motivated and described. Simulation results show that the heuristic algorithm gives near-optimal results in real-time, allowing it to be used for large problem sizes and extended to dynamic scenarios.
A general methodology has been developed for the design of a robust control law for a family of lightly damped second order problems. In this research effort, the passivity approach has been extended to systems having non-collocated input/output pairs by introducing an observer that incorporates the nominal dynamical model of the plant. The developed passive observer-based control law emulates numerous dynamic vibration absorbers which are tuned to a targeted frequency using classical methods and the tuning ratios are time-invariant. However, the uniqueness of this approach is that the damping parameters of the emulated absorbers are continuously varied by means of a fuzzy logic control algorithm to provide near minimum-time suppression of vibration. The developed approach is applied to both several benchmarks in the field of structural dynamics as well as experiments using piezo-ceramic sensors and actuators. Results show that this methodology provides stability and performance robustness on the one hand as well as requiring relatively low amount of actuation authority for desired nominal plant closeloop behavior.
Fire is a natural component of many ecosystems but wildland fires often do pose serious threats to public safety, properties and natural resources. Forest fire acts as a dominant factor in reshaping of terrain and change of the ecosystem of a particular area. The total damage due to wildland fire shows an increasing trend over the past decade. Forest Fire Decision Support Systems (FFDSS) have been developed for the last thirty years all over the world that supplies valuable information on forest fire detection, fire behavior and other aspects of forest fires but lacks in developing intelligent fire suppression strategies. In this paper, an effort has been made to generate intelligent fire suppression strategies with efficient resource allocation using the Genetic Algorithm based optimization tool in a heterogeneous and uncertain scenario. The goal of this research is to perform intelligent resource allocation along with the generation of optimal firelines that minimizes the total burned area due to wildland fire. The solutions generated at each generations of the Genetic Algorithm (GA) are used to build the firelines in a heterogeneous terrain where advanced forest fire propagation model is used to evaluate the fitness values of each generated solutions. The optimal firelines thus obtained through the Simulation-Optimization technique minimizes the total damage due to wildland fire and eliminates the chance of any fire escape i.e., firefront reaching the fireline positions before they are built. Such techniques integrated with the existing FFDSS hold promise in effectively controlling forest fires.
This work presents a methodology for real-time estimation of wildland fire growth, utilizing a fire growth model based on a set of partial differential equations for prediction, and harnessing concepts of space-time Kalman filtering and Proper Orthogonal Decomposition techniques towards low dimensional estimation of potentially large spatio-temporal states. The estimation framework is discussed in its criticality towards potential applications such as forest fire surveillance with unmanned systems equipped with onboard sensor suites. The effectiveness of the estimation process is evaluated numerically over fire growth data simulated using a well-established fire growth model described by coupled partial differential equations. The methodology is shown to be fairly accurate in estimating spatio-temporal process states through noise-ridden measurements for real-time deployability.
This study introduces the technique of Genetic Fuzzy Trees (GFTs) through novel application to an air combat control problem of an autonomous squadron of Unmanned Combat Aerial Vehicles (UCAVs) equipped with next-generation defensive systems. GFTs are a natural evolution to Genetic Fuzzy Systems, in which multiple cascading fuzzy systems are optimized by genetic methods. In this problem a team of UCAV's must traverse through a battle space and counter enemy threats, utilize imperfect systems, cope with uncertainty, and successfully destroy critical targets. Enemy threats take the form of Air Interceptors (AIs), Surface to Air Missile (SAM) sites, and Electronic WARfare (EWAR) stations. Simultaneous training and tuning a multitude of Fuzzy Inference Systems (FISs), with varying degrees of connectivity, is performed through the use of an optimized Genetic Algorithm (GA). The GFT presented in this study, the Learning Enhanced Tactical Handling Algorithm (LETHA), is able to create controllers with the presence of deep learning, resilience to uncertainties, and adaptability to changing scenarios. These resulting deterministic fuzzy controllers are easily understandable by operators, are of very high performance and efficiency, and are consistently capable of completing new and different missions not trained for.
Comparison of approximate approaches to solving the Travelling Salesman Problem and its application to UAV swarming. International Journal of Unmanned Systems Engineering. 3(1): 1-16. The Travelling Salesman Problem (TSP) is a widely researched Non-deterministic Polynomial-time hard optimization problem with a range of important applications in a wide spectrum of disciplines including aerospace engineering. In this paper, a comparison of different approaches to solve the TSP and also its application towards swarming of UAVs is considered. The objective of the TSP is to determine the optimal route associated with the shortest tour connecting all targets just once. Genetic Algorithms (GA) are one of the most widely applied techniques for solving this class of optimization problems. Two other techniques, 2-opt and Particle Swarm Optimization, are used and the results are compared with those obtained using GA. The comparison is made for different numbers of targets, using salient figures of merit such as computational time required and the cost function which is the minimum solution (distance) obtained. Results show that the 2-opt approach with the closest neighbour as initial starting point for the search yields superior performance. In the Multiple Travelling Salesman Problem, we propose a cluster-first approach which allocates each specific UAV to a subset of targets. The 200 targets are divided into four clusters corresponding to the four UAVs and then TSP algorithms like 2-opt and GA are employed to solve each cluster. This approach drastically reduces the computational time and also gives much better results than the conventional technique of directly applying GA over the 200 targets.
Severe congenital neutropenia (SCN) is often associated with inherited heterozygous point mutations in ELANE, which
encodes neutrophil elastase (NE). However, a lack of appropriate models to recapitulate SCN has substantially hampered
the understanding of the genetic etiology and pathobiology of this disease. To this end, we generated both normal and SCN
patient–derived induced pluripotent stem cells (iPSCs), and performed genome editing and differentiation protocols that
recapitulate the major features of granulopoiesis. Pathogenesis of ELANE point mutations was the result of promyelocyte
death and differentiation arrest, and was associated with NE mislocalization and activation of the unfolded protein
response/ER stress (UPR/ER stress). Similarly, high-dose G-CSF (or downstream signaling through AKT/BCL2) rescues
the dysgranulopoietic defect in SCN patient–derived iPSCs through C/EBPβ-dependent emergency granulopoiesis. In
contrast, sivelestat, an NE-specific small-molecule inhibitor, corrected dysgranulopoiesis by restoring normal intracellular
NE localization in primary granules; ameliorating UPR/ER stress; increasing expression of CEBPA, but not CEBPB; and
promoting promyelocyte survival and differentiation. Together, these data suggest that SCN disease pathogenesis includes
NE mislocalization, which in turn triggers dysfunctional survival signaling and UPR/ER stress. This paradigm has the
potential to be clinically exploited to achieve therapeutic responses using lower doses of G-CSF combined with targeting to
correct NE mislocalization.
Chromosome 5q deletions (del[5q]) are common in
high-risk (HR) myelodysplastic syndrome (MDS) and
acute myeloid leukemia (AML); however, the gene
regulatory networks that sustain these aggressive
diseases are unknown. Reduced miR-146a expression
in del(5q) HR MDS/AML and miR-146a/ hematopoietic
stem/progenitor cells (HSPCs) results in
TRAF6/NF-kB activation. Increased survival and proliferation
of HSPCs from miR-146alow HR MDS/AML is
sustained by a neighboring haploid gene, SQSTM1
(p62), expressed from the intact 5q allele. Overexpression
of p62 from the intact allele occurs through
NF-kB-dependent feedforward signaling mediated
by miR-146a deficiency. p62 is necessary for
TRAF6-mediated NF-kB signaling, as disrupting the
p62-TRAF6 signaling complex results in cell-cycle arrest
and apoptosis of MDS/AML cells. Thus, del(5q)
HR MDS/AML employs an intrachromosomal gene
network involving loss of miR-146a and haploid overexpression
of p62 via NF-kB to sustain TRAF6/NF-kB
signaling for cell survival and proliferation. Interfering
with the p62-TRAF6 signaling complex represents a
therapeutic option in miR-146a-deficient and aggressive
Patients in organ failure of vascular origin have increased circulating hematopoietic stem cells and
progenitors (HSC/P). Plasma levels of angiotensin II (Ang-II), are commonly increased in
vasculopathies. Hyperangiotensinemia results in activation of a very distinct Ang-II receptor set,
Rho-family GTPase members, and actin in bone marrow endothelial cells (BMEC) and HSC/P,
which results in decreased membrane integrin activation in both BMEC and HSC/P, and in HSC/P
de-adhesion and mobilization. The Ang-II effect can be reversed pharmacologically and
genetically by inhibiting Ang-II production or signaling through BMEC AT2R, HSCP AT1R/
AT2R or HSC/P RhoA, but not by interfering with other vascular tone mediators.
Hyperangiotensinemia and high counts of circulating HSC/P seen in sickle cell disease (SCD) as a
result of vascular damage, is significantly decreased by Ang-II inhibitors. Our data define for the
first time the role of Ang-II HSC/P traffic regulation and redefine the hematopoietic consequences
of anti-angiotensin therapy in SCD.
Overnight, room temperature hold
(ONH) of whole blood before component processing
offers several benefits. This study evaluated the storage
and in vivo recovery characteristics of ONH red blood
cells (RBCs) stored in additive solution-7 (AS-7).
PM-18. EGFR-STAT3 ACTIVATES b-CATENIN SIGNALING TO
DRIVE NEUROFIBROMA INITIATION IN NF1, AND PLAYS A
ROLE IN TUMOR MAINTENANCE
Nancy Ratner1, Vincent Keng2, Deanna M. Patmore1, Jed K. Kendall1,
Edwin Jousma1, Kwangmin Choi1, Danhua Fan2, Eric B. Schwartz2, James
R. Fuchs2, Yuanshu Zou2, Mi-Ok Kim1, Eva Dombi5, David E. Levy6, Jose
A. Cancelas1, Anat Stemmer-Rachamimov4, Robert J. Spinner3, and David
Cincinnati Children’s, Cincinnati, OH, USA; 2
Minnesota, Minneapolis, MN, USA; 3
Mayo Clinic, Rochester, MN, USA; 4
Massachusetts General Hospital, Boston, MA, USA; 5
Institute Pediatric Branch, Bethesda, MD, USA; 6
New York University School
of Medicine, New York, NY, USA
To identify genes and signaling pathways that drive peripheral nerve tumor
initiationand growth beyond the Ras-MAPK pathwaywe used unbiased insertional
mutagenesis screening. We identified Stat3 as a potential driver of
Neurofibromatosis type 1 neurofibroma. Targeted genetic deletion of Stat3
in Schwann cell precursors (SCPs) and Schwann cells (SCs) largely prevented
neurofibroma formation, and self-renewal of tumor initiating cells. Genetic
gain- and loss-of-function identified EGFR as the major upstream regulator
of P-Stat3 in mouse and human neurofibroma SCP and in neurofibroma initiation;
IL-6 reinforced EGFR/Jak/Stat signaling. Preclinical tests of a Jak2/
Stat3 inhibitor reduced established neurofibroma growth, supporting an additional
role for Stat3 in benign nerve tumor maintenance. Unexpectedly, downstream
of Stat3, we identified b-catenin, and b-catenin expression rescued
phenotypic effects of Stat3 loss in SCPs. Phosphorylated STAT3 (Y705) and
b-catenin were strongly correlated in NF1 human plexiform neurofibromas.
The data support testing of JAK/STAT inhibition and Wnt/ b-catenin
pathway inhibition in neurofibroma therapeutic trials. Supported by: NIH
R01 NS28840 to N.R. and NIH P50 NS057531 to N.R. and D.L.), a
DAMD New Investigator Award (W81XWH-11-1-0259) and an Ohio State
University Comprehensive Cancer Center Pelotonia Idea Grant (to J.W.).
The American Cancer Society (IRG-67-003-44) supported J.R.F.
Wu et al. map an Nf1-Stat3-Arid1b/ b-catenin pathway that initiates
Neurofibromatosis type 1 (Nf1) neurofibromas, using unbiased
insertional mutagenesis screening. Stat3 transcriptionally represses Gsk3b and Arid1b, thereby activating b-catenin in Schwann cell precursors and resulting in neurofibroma initiation and maintenance.
Stat3-mediated modification plays a role in early tumorigenesis.
The methods and outcome of a senior undergraduate project related to the control of a turbulent cylinder wake flow using plasma actuators are summarized in this article. The study integrates computational fluid dynamics (CFD) with experimentation and combines fluid mechanics with flow control research, crossing the boundaries between engineering disciplines.Comput. Appl. Eng. Educ.
This work presents a methodology for real-time estimation of wildland fire growth, utilizing afire growth model based on a set of partial differential equations for prediction, and harnessing concepts of space-time Kalman filtering and Proper Orthogonal Decomposition techniques towards low dimensional estimation of potentially large spatio-temporal states. The estimation framework is discussed in its criticality towards potential applications such as forest fire surveillance with unmanned systems equipped with onboard sensor suites. The effectiveness of the estimation process is evaluated numerically over fire growth data simulated using a well-established fire growth model described by coupled partial differential equations. The methodology is shown to be fairly accurate in estimating spatio-temporal process states through noise-ridden measurements for real-time deploy ability.
Breakthroughs in genetic fuzzy systems, most notably the development of the Genetic Fuzzy Tree methodology, have allowed fuzzy logic based Artificial Intelligences to be developed that can be applied to incredibly complex problems. The ability to have extreme performance and computational efficiency as well as to be robust to uncertainties and randomness, adaptable to changing scenarios, verified and validated to follow safety specifications and operating doctrines via formal methods, and easily designed and implemented are just some of the strengths that this type of control brings. Within this white paper, the authors introduce ALPHA, an Artificial Intelligence that controls flights of Unmanned Combat Aerial Vehicles in aerial combat missions within an extreme-fidelity simulation environment. To this day, this represents the most complex application of a fuzzy-logic based Artificial Intelligence to an Unmanned Combat Aerial Vehicle control problem. While development is on-going, the version of ALPHA presented withinwas assessed by Colonel (retired)Gene Lee who described ALPHA as “the most aggressive, responsive, dynamic and credible AI (he’s) seen-to-date.” The quality of these preliminary results in a problem that is not only complex and rife with uncertainties but also contains an intelligent and unrestricted hostile force has significant implications for this type of Artificial Intelligence. This work adds immensely to the body of evidence that this methodology is an ideal solution to a very wide array of problems.
For a Timoshenko beam model the equations of motion, representing the anisotropic continuum model of a two-dimensional, latticed, large space structure, are extended to include coupling between the extensional, shear and bending modes. This analytical model, applied to a 20-bay, orthogonal, tetrahedral, cantilevered truss structure, is used to determine the transient response when subjected to a unit impulse. It is demonstrated that for beam-like structures having a fixed bending stiffness and beam mass an increase in diagonal stiffness, on account of the stiffness of the vertical girder, leads to a rise in the transverse shear rigidity. This results in higher natural frequencies and a reduction in peak displacement. In addition, in an asymmetrical truss configuration, coupling between the extensional and shear modes raises the maximum peak displacement compared to that obtained for a symmetric truss. The model is modified to investigate the introduction of passive damping in the form of several dynamic vibration absorbers. For a fixed absorber mass budget, a simple yet efficient absorber parameter optimization procedure, based on the classical steady state criteria of a 2-DOF system, is developed to design several absorbers each tuned to a different modal frequency. It is found that inclusion of transverse shear rigidity, as a design parameter in damping augmentation studies, reduces settling time for predetermined maximum peak displacements.
The present study deals with an AFCA (Adaptive Fuzzy Control Algorithm) for an Euler-Bemoulli approximation of a two-dimensional version of a cantilever beam-like orthogonal tetrahedral space truss. Transient disturbances, modeled as a unit impulse, excite all the modes of the beam. The resulting transverse displacement at the free end of the beam and its corresponding rate are observed by sensors placed there, and active control of the beam is provided by a collocated force actuator.
A design methodology, based on fuzzy logic which assumes no a priori knowledge of plant dynamics, for the closed-loop control algorithm results in relatively quick settling times, low overshoots and dying out of vibration within a few seconds. The control algorithm is enhanced and made much faster by eliminating the need of repeatedly solving the set of differential equations of motion of an emulated dynamic vibration absorber. When the control force is turned off after a mere 15 seconds, almost all the vibrational energy is dissipated as the beam returns to its undisturbed state throughout its length. In addition, the performance of the AFCA is insensitive to varying initial conditions. To examine the robustness of the control system to changes in the temporal dynamics of the cantilever beam, the transient disturbance response to a considerably perturbed plant is simulated. The Young's modulus of the beam was raised as well as lowered by 60%, substantially perturbing the natural frequencies of vibration compared to the nominal plant. The AFCA provided similar settling times and rates of vibrational energy dissipation, satisfying the aim of plant model independence.
The present study deals with an AFCA (Adaptive Fuzzy Control Algorithm) for an Euler-Bernoulli approximation of a two-dimensional version of a cantilever beam-like orthogonal tetrahedral space truss. Transient disturbances, modeled as a unit impulse, excite all the modes of the beam. The resulting transverse displacement at the free end of the beam and its corresponding rate are observed by sensors placed there, and active control of the beam is provided by a collocated force actuator.
A design methodology for the closed-loop control algorithm that is independent of an exact mathematical model (space-state model, F.E.M., etc.) of plant dynamics and which is based on fuzzy logic is presented. First, the behavior of the open-loop system is observed. Then, the control force applied to the system emulates the behavior of a dynamic vibration absorber which is tuned to the measured fundamental frequency. This approach not only assures inherent stability associated with passive absorbers, but also circumvents the phenomenon of modal spillover. The damping and the mass ratios of the absorber adapt themselves by using a fuzzy decision-making process. This results in relatively quick settling times, low overshoots and dying out of vibration within a few seconds.
When the control force is turned off after a mere 16 seconds, almost all the vibrational energy is dissipated. In addition, the performance of the AFCA is insensitive to varying initial conditions. To demonstrate the robustness of the control system to changes in the temporal dynamics of the cantilever beam, the transient response to a considerably perturbed plant is simulated. The Young's modulus of the beam was raised as well as lowered substantially, thereby significantly perturbing the natural frequencies of vibration. The mode shapes, however, remain unchanged. For these cases, too, the AFCA provides similar settling times and rates of vibrational energy dissipation.
The control of exible structures employing the passivity approach has been extended to systems having noncollocated input/output pairs by introducing an observer that incorporates the nominal dynamical model of the plant. The passive observer-based control is applied to the American Control Conference benchmark problem, whereby, the control force emulates a dynamic vibration absorber attached to a virtual wall with passive control elements (spring, mass, and dashpot). The springs and mass elements of the controller are constant, whereas the damping coef cients are selected as time dependent in an attempt to choose continuously the most appropriate amount of damping in compliance with the design goals. A novel approach is introduced, whereby the passive observer-based control law is modi ed by varying the damping coef cient of the virtual dashpot by means of an adaptive fuzzy logic algorithm. This modi ed system exhibits quick settling times and desirable performance characteristics. Results from the statistical robustness analysis for the developed controller are compared to 10 other (linear) solutionsof the benchmarkproblem. The comparisonis based onrobust stability, robust performance (settling time), and control effort. The results obtained by the adaptive fuzzy logic algorithm are superior to those obtained by all other methods, and, consequently, further application of the fuzzy algorithm is advocated.
The present investigation deals with the application of an Adaptive Fuzzy Control Algorithm for active vibration control of an experimental flexible beam. The two-dimensional model of the experimental cantilever beam, given by an orthogonal tetrahedral space truss, represents a slender cantilever aluminum (7075-T6) beam of rectangular cross-section (1145 × 60 × 1.95 mm3). A variety of transient disturbances are introduced to excite the first four modes of the beam. The resulting transverse displacements are observed by a single sheet (50 × 50 mm2) of piezoceramic material placed at the clamped end of the beam. Active control of the beam is provided by one, two or three identical sheets of piezoceramic material collocated with the sensor. The control moments applied by the piezoceramic actuator are made to emulate the behavior of a discrete dynamic vibration absorber. The virtual absorber is tuned to the fundamental frequency using classical methods and the tuning ratios are time-invariant. However, the uniqueness of this approach is that the damping parameters of the emulated absorber are continuously varied by means of a fuzzy logic control algorithm to provide near minimum-time suppression of vibration. It is demonstrated that application of this methodology allows for its real-time implementation and provides relatively quick settling times in the closed-loop.
In this study a general approach is introduced for the design of a robust control law for suppression of structure borne vibration. This control law is based on a passive design in the form of dynamic vibration absorbers. Passive absorbers minimize vibration at a speci c frequency, but their performance is improved by introducing adaptive tuning of the absorber. An adaptive dynamic vibration absorber is tuned to the forcing frequency, using classical methods. The tuning ratio is time varying and adapts itself to variations in the forcing frequency. However, the uniqueness of the approach in this study is that the damping parameter of the absorber is continuously varied by means of a fuzzy-logic control algorithm to provide a lower sound pressure level. The inputs of the fuzzy control law are the displacement and velocity of the main structure. The effectiveness of the control algorithm for active vibration control is demonstrated using MATLAB® simulations of a single-degree-of-freedom plant. This methodology provides superior performance in the presence of signi cant mistuning compared to a more conventional approach.
Closed-loop control strategies were studied experimentally at low Reynolds and incompressible Mach numbers using periodic excitation to vector a turbulent jet. Vectoring was achieved by attaching a short, wide-angle diffuser at the jet exit and introducing periodic excitation from a slot covering one quadrant of the circumference of the round turbulent jet. Closed-loop control methods were applied to transition quickly and smoothly between different jet de ection angles. The frequency response of the zero-mass- ux piezoelectric actuatorwas at to about 0.5 kHz, but the jet responds up to 30–50 Hz only. This is still an order of magnitude faster than conventional thrust vectoring mechanism. System identi cation procedures were applied to approximate the system’s transfer function. A linear controller was designed that enabled fast and smooth transitions between stationary de ection angles and maintained desired jet vectoring angles under varying system conditions. The linear controller was tested over the entire range of available de ection angles, and its performance is evaluated and discussed.
For feedback control using low-dimensional proper orthogonal decomposition (POD) models, the mode amplitudes of the POD mode coefficients need to be estimated based on sensor readings. This paper is aimed at suppressing the von Kairman vortex street in the wake of a circular cylinder using a low-dimensional approach based on POD. We compare sensor placement methods based on the spatial distribution of the POD modes to arbitrary ad hoc methods. Flow field data were obtained from Navier-Stokes simulation as well as particle image velocimetry (PIV) measurements. A low-dimensional POD was applied to the snapshot ensembles from the experiment and simulation. Linear stochastic estimation was used to map the sensor readings of the velocity field on the POD mode coefficients. We studied 53 sensor placement configurations, 32 of which were based on POD eigenfunctions and the others using ad hoc methods. The effectiveness of the sensor configurations was investigated at Re = 100 for the computational fluid dynamic data, and for a Reynolds number range of 82-99 for the water tunnel PIV data. Results show that a five-sensor configuration can keep the root mean square estimation error, for the amplitudes of the first two modes to within 4% for simulation data and within 10% for the PIV data. This level of error is acceptable for a moderately robust controller The POD-based design was found to be simpler. more effective, and robust compared to the ad hoc methods examined.
A short computational program was undertaken to evaluate the effectiveness of a closed-loop control strategy for the stabilization of an unstable bluff-body flow. In this effort, the non-linear one-dimensional Ginzburg–Landau wake model at 20% above the critical Reynolds number was studied. The numerical model, which is a non-linear partial differential equation with complex coefficients, was solved using the FEMLAB®/MATLAB® software packages and validated by comparison with published literature. At first, a model independent approach was attempted for wake suppression using feedback control. The closed-loop system was controlled using a conventional proportional-integral-derivative (PID) controller as well as a non-linear fuzzy controller. A single sensor is used for feedback, and the actuator is represented by altering the boundary conditions of the cylinder. Simulation results indicate that for a single sensor scheme, the increase in the sophistication of the control results in significantly shorter settling times. However, there is only a marginal improvement concerning the suppression of the wake at higher Reynolds numbers. The feedback control design was then augmented by switching over to a model-dependent controller. Based on computationally generated data obtained from solving the unforced wake, a low-dimensional model of the wake was developed and evaluated. The low-dimensional model of the unforced Ginzburg–Landau equation captures more than 99.8% of the kinetic energy using just two modes. Two sensors, placed in the absolutely unstable region of the wake, are used for real-time estimation of the first two modes. The estimator was developed using the linear stochastic estimation scheme. Finally, the loop is closed using a PID controller that provides the command input to the variable boundary conditions of the model. This method is relatively simple and easy to implement in a real-time scenario. The control approach, applied to the 300 node FEMLAB® model at 20% above the unforced critical Reynolds number stabilizes the entire wake. Compared to the model-independent controllers, the controller based on the low-dimensional model is far more effective in the suppression of the wake at higher Reynolds numbers. Furthermore, while the latter approach employs only the estimated temporal amplitude of the first mode of the imaginary part of the amplitude, all higher modes are stabilized. This suggests that the higher order modes are caused by a secondary instability that is suppressed once the primary instability is controlled.
The effectiveness of a sensor configuration for feedback flow control on the wake of a circular cylinder is investigated in both direct numerical simulation as well as in a water tunnel experiment. The research program is aimed at suppressing the von Kármán vortex street in the wake of a cylinder at a Reynolds number of 100. The design of sensor number and placement was based on data from a laminar two-dimensional simulation of the Navier–Stokes equations for the unforced condition. A low-dimensional proper orthogonal decomposition (POD) was applied to the vorticity calculated from the flow field and sensor placement was based on the intensity of the resulting spatial eigenfunctions. The numerically generated data was comprised of 70 snapshots taken over three cycles from the steady state regime. A linear stochastic estimator (LSE) was employed to map the velocity data to the temporal coefficients of the reduced order model. The capability of the sensor configuration to provide accurate estimates of the four low-dimensional states was validated experimentally in a water tunnel at a Reynolds number of 108. For the experimental wake, a sample of 200 particle image velocimetry (PIV) measurements was used. Results show that for experimental data, the root mean square estimation error of the estimates of the first two modes was within 6% of the desired values and for the next two modes was within 20% of the desired values. This level of error is acceptable for a moderately robust controller.
The effect of feedback flow control on the wake of a circular cylinder at a Reynolds number of 100 is investigated in direct numerical simulation. The control approach uses a low-dimensional model based on proper orthogonal decomposition (POD). The controller applies linear proportional and differential feedback to the estimate of the first POD mode. The range of validity of the POD model is explored in detail. Actuation is implemented as displacement of the cylinder normal to the flow. It is demonstrated that the threshold peak amplitude below which the control actuation ceases to be effective is in the order of 5% of the cylinder diameter. The closed-loop feedback simulations explore the effect of both fixed-phase and variable-phase feedback on the wake. Whereas fixed-phase feedback is effective in reducing drag and unsteady lift, it fails to stabilize this state once the low drag state has been reached. Variable-phase feedback, however, achieves the same drag and unsteady lift reductions while being able to stabilize the flow in the low drag state. In the low drag state, the near wake is entirely steady, whereas the far wake exhibits vortex shedding at a reduced intensity. A drag reduction of 15% of the drag was achieved, and the unsteady lift force was lowered by 90%.
The effectiveness of a small array of body-mounted sensors, for estimation and eventually feedback flow control of a D-shaped cylinder wake is investigated experimentally. The research is aimed at suppressing unsteady loads resulting from the von-Kármán vortex shedding in the wake of bluff-bodies at a Reynolds number range of 100–1,000. A low-dimensional proper orthogonal decomposition (POD) procedure was applied to the stream-wise and cross-stream velocities in the near wake flow field, with steady-state vortex shedding, obtained using particle image velocimetry (PIV). Data were collected in the unforced condition, which served as a baseline, as well as during influence of forcing within the “lock-in” region. The design of sensor number and placement was based on data from a laminar direct numerical simulation of the Navier-Stokes equations. A linear stochastic estimator (LSE) was employed to map the surface-mounted hot-film sensor signals to the temporal coefficients of the reduced order model of the wake flow field in order to provide accurate yet compact estimates of the low-dimensional states. For a three-sensor configuration, results show that the estimation error of the first two cross-stream modes is within 20–40% of the PIV-generated POD time coefficients. Based on previous investigations, this level of error is acceptable for a moderately robust controller required for feedback flow control.
For the systematic development of feedback flow controllers, a numerical model that captures the dynamic behaviour of the flow field to be controlled is required. This poses a particular challenge for flow fields where the dynamic behaviour is nonlinear, and the governing equations cannot easily be solved in closed form. This has led to many versions of low-dimensional modelling techniques, which we extend in this work to represent better the impact of actuation on the flow. For the benchmark problem of a circular cylinder wake in the laminar regime, we introduce a novel extension to the proper orthogonal decomposition (POD) procedure that facilitates mode construction from transient data sets. We demonstrate the performance of this new decomposition by applying it to a data set from the development of the limit cycle oscillation of a circular cylinder wake simulation as well as an ensemble of transient forced simulation results. The modes obtained from this decomposition, which we refer to as the double POD (DPOD) method, correctly track the changes of the spatial modes both during the evolution of the limit cycle and when forcing is applied by transverse translation of the cylinder. The mode amplitudes, which are obtained by projecting the original data sets onto the truncated DPOD modes, can be used to construct a dynamic mathematical model of the wake that accurately predicts the wake flow dynamics within the lock-in region at low forcing amplitudes. This low dimensional model, derived using nonlinear artificial neural network based system identification methods, is robust and accurate and can be used to simulate the dynamic behaviour of the wake flow. We demonstrate this ability not just for unforced and open-loop forced data, but also for a feedback-controlled simulation that leads to a 90% reduction in lift fluctuations. This indicates the possibility of constructing accurate dynamic low-dimensional models for feedback control by using unforced and transient forced data only.
The ability to spatially alter both the amount of body force along the span of a plasma actuator and the angle of the resulting jet relative to the surface has been demonstrated. A dielectric barrier discharge plasma actuator consists of two electrodes separated by a dielectric barrier, which imparts momentum to the surrounding fluid parallel to the dielectric. To investigate a technique to shape the spanwise body force created by the plasma actuator, a control volume momentum balance was used. By shaping the buried electrode along the span of the actuator, the local volume of plasma generated can be controlled, which is related to the local body force. Pressure measurements were taken in the boundary layer behind the actuator to calculate the momentum imparted to the flow at various spanwise locations corresponding to different electrode widths. Particle image velocimetry data were then used to show that spatially varying, steady jets could be created with the use of only one actuator by varying the width of the buried electrode in a quiescent flow. The angle of the jet created, relative to the dielectric, by a plasma synthetic jet is also investigated. By pointing two plasma actuators at each other, an inverted impinging jet can be created as a result of the two independent jets colliding. By altering the strength of one of the jets relative to the other, the angle of separation can be changed. Particle image velocimetry data were taken to show the effects of altering the voltage (strength) applied to one of the actuators relative to the other. It was found that, with this method, jet vectoring could be achieved. The angle of the jet could be controlled a full 180 deg through small changes in the voltage applied to the electrodes, also in a quiescent flow.
Mazes have intrigued the human mind for thousands of years, and have been used to measure cognitive abilities of laboratory animals. In recent years, mazes have been used to examine the artificial intelligence of robots by observing their ability to traverse mazes using algorithm for maze exploration and exploitation.A simulation of a multi-agent system is used to demonstrate the benefits of utilizing a group of several robots in maze exploration. Using a behavioral algorithm based on Tarry’s algorithm, it is shown that the group performance improves and becomes more robust as the number of robots increases. In addition, the amount of data transfer required for group coordination can be minimized to a small set of data items, which is independent of either the number of robots in the group or the maze size.As a result, the above multi-agent approach can be scaled up to mazes or groups of any size, as indicated by the results of the MATLAB-based simulation.
Uninhabited aerial vehicles provide numerous advantages in fighting wildland fires that include persistent operation and elimination of humans from performing what can be dull, dangerous, and dirty work. Multiple cooperating uninhabited aerial vehicles can potentially bring about a paradigm shift in the way we fight complex wildland fires. This paper investigates algorithmic development for cooperative control of a number of uninhabited aerial vehicles engaged in fighting a wildland fire. The paper considers two tasks to be performed by a group of uninhabited aerial vehicles: 1) Cooperative tracking of a fire front for accurate situational awareness, and 2) cooperative, autonomous fire fighting using fire suppressant fluid. The scenario considered in this paper makes the following assumptions: information regarding the location of the fire and position of all uninhabited aerial vehicles is made available to each uninhabited aerial vehicle; and each uninhabited aerial vehicle is equipped with unlimited fire suppressant fluid which extinguishes fire in a circle of specified area directly beneath it. This paper formulates these two tasks of fire fighting based upon optimization of respective utility functions, develops a decentralized control method for the cooperative uninhabited aerial vehicles, and analyzes the system for its stability and its ability to carry out the tasks. The proposed strategies have been verified with the help of extensive simulations. Although simplifying assumptions have been made, this preliminary study presents a framework for path planning and cooperative control of multiple uninhabited aerial vehicles engaged in gathering data and actively fighting forest fires.
Low-dimensional models have proven essential for feedback control and estimation of flow fields. While feedback control based on global flow estimation can be very efficient, it is often difficult to estimate the flow state if structures of very different length scales are present in the flow. The conventional snapshot-based proper orthogonal decomposition (POD), a popular method for low-order modeling, does not separate the structures according to size, since it optimizes modes based on energy. Two methods are developed in this study to separate the structures in the flow based on size. One of them is Hybrid Filtered POD method and the second one is 3D FFT-based Filtered POD approach performed using a fast Fourier transform (FFT)-based spatial filtering. In both the methods, a spatial low-pass filter is employed to precondition snapshot sets before deriving POD modes. Three-dimensional flow data from the simulation of turbulent flow over a circular cylinder wake at Re=20000 is used to evaluate the performance of the two methods. Results show that both the FFT-based 3D Filtered POD and Hybrid Filtered POD are able to capture the large-scale features of the flow, such as the von Karman vortex street, while not being contaminated by small-scale turbulent structures present in the flow.
Tasks allocation is a fundamental problem in multiagent systems. We formulate the problem as a multiple traveling salesmen problem (MTSP), which is an extension to the well known traveling salesman problem (TSP), both considered to be NP-hard combinatorial optimization problems. We propose a solution in which agents interact in an economic market to win tasks situated in an environment. The agents strive to minimize required costs, defined as either the total distance traveled by all agents or the maximum distance traveled by any agent. Using a set of simple market operations, the agents come up with a solution for task allocation. In this work we examine the processing speed of the market-based solution (MBS), as well as the quality vs. optimal solutions achieved using enumeration for a 3 agents by 8 tasks scenario. We show that the MBS is both quick and close to optimal. We then show that the MBS can be scaled to more complicated problems, by comparing its results with results from genetic algorithm (GA) and clustering. We also show the robustness of the MBS to changes in the scenario, e.g. the addition and removal of tasks or agents.
This research was conducted within the framework of a National Science Foundation sponsored summer Research Experience for Undergraduate (REU) students. This research considers small-scale and mathematical models of simple one-story structures that are subjected to free and base-motion excitations and installed with and without passive damping devices to gain an understanding of their dynamic behavior while reviewing active and semi-active damping means being applied and researched today. Using computer programming and numerical methods, the goal is to understand and counteract catastrophic disasters to structures caused by earthquakes. The research is broken down into a number of MATLAB simulations and experiments in order to understand basic dynamic and control features required to design earthquake resilient buildings. These experiments include free vibration experiments to test for the stiffness of columns for different heights and to test for the natural frequency and damping ratio of a one-story structure under different mass loads. Active PD control was then applied to an experimental system experiencing accelerations attributed to the Northridge 1994, Kobe 1995, El Centro 1940, and Mendocino 1992 earthquakes. Robustness comparisons were made between (1) P control; (2) D control; and (3) PD control for the above earthquake inputs to the shaker. A fuzzy logic controller was developed to effectively control transient vibrations. The uniqueness of this control concept is that the fuzzy control continuously varies the damping characteristics of a semi-active tuned mass damper (TMD). It was concluded that a fuzzy logic based TMD was more effective than a regular passive TMD, by providing half the settling times.
Feedback flow control of the wake of a circular cylinder at a Reynolds number of 100 is an interesting and challenging benchmark for controlling absolute instabilities associated with bluff body wakes. A two dimensional computational fluid dynamics simulation is used to develop low-dimensional models for estimator design. Actuation is implemented as displacement of the cylinder normal to the flow. The estimation approach uses a low dimensional model based on a truncated 6 mode Double Proper Orthogonal Decomposition (DPOD) applied to the streamwise velocity component of the flow field. Sensor placement is based on the intensity of the resulting spatial modes. A non-linear Artificial Neural Network Estimator (ANNE) was employed to map the velocity data to the mode amplitudes of the DPOD model. For a given four sensor configuration, developed using a previously validated strategy, ANNE performed better than two state-of-the-art approaches, namely, a Quadratic Stochastic Estimator (QSE) and a Linear Stochastic Estimator with time delays (DSE).
There are a variety of scenarios in which the mission objectives rely on an unmanned aerial vehicle (UAV) being capable ofmaneuvering in an environment containing obstacles in which there is little prior knowledge of the surroundings. With an appropriate dynamicmotion planning algorithm, UAVs would be able tomaneuver in any unknown environment towards a target in real time. This paper presents a methodology for two-dimensional motion planning of a UAV using fuzzy logic. The fuzzy inference system takes information in real time about obstacles (if within the agent’s sensing range) and target location and outputs a change in heading angle and speed. The FL controller was validated, andMonte Carlo testing was completed to evaluate the performance.Not only was the path traversed by the UAV often the exact path computed using an optimal method, the low failure rate makes the fuzzy logic controller (FLC) feasible for exploration. The FLC showed only a total of 3% failure rate, whereas an artificial potential field (APF) solution, a commonly used intelligent control method, had an average of 18% failure rate. These results highlighted one of the advantages of the FLC method: its adaptability to complex scenarios while maintaining low control effort.
The standard curriculum for Aerospace Engineering students at the University of Cincinnati includes AEEM361 Integrated Aircraft Engineering. The goal of this course is to instruct students in the tools and methodology of aircraft design. The integrated aspects of aircraft design are underscored by introducing prejunior (between sophomore and junior) students to the state-of-the-art morphing technology, inspired by bat and bird flight, which can enable an aircraft to adapt its shape to best suit the flight condition thereby enhancing mission performance. In this article, we present the development of unique software tools, which provide undergraduates an opportunity to design airfoils for morphing aircraft. Morphing is introduced in the form of “on demand” camber as well as sweep change with the aim of improving aerodynamic efficiency for a multiobjective (several design points) mission profile. The Global Hawk UAV mission in general and its LRN1015 airfoil in particular is in focus due to the relative long mission times spent at the two different flight conditions, namely high-speed dash and low-speed loiter. We are using several tools to virtually simulate a morphing wing including XFOIL to perform fast and relatively accurate two-dimensional steady-flow simulations of different morphed configurations using a camber-controlled morphed wing to maneuver. In this article we detail AeroMorph, the educational MATLAB-based tool developed for design of a camber-controlled morphing of airfoils with the aim of improving aerodynamic efficiency and exploration of the basic relationships between flap deflection and airfoil morphing based on a camber change.
Over the past 10 years there has been a growing need to introduce closed-loop control technology for vibration suppression of buildings subject to wind or earthquake disturbances. This paper deals with the investigation of the effectiveness of a fuzzy logic based time variable damping tuned mass damper (TMD) on a building structure undergoing free and forced vibrations. The uniqueness of this approach is the application of a robust, nonlinear fuzzy based controller to emulate a time-optimal control strategy. Fuzzy logic based time variable damping is introduced into a semi-active TMD in order to enhance its performance in the vibration suppression of buildings. First, a single story structure for three different vibration suppression approaches is studied. The fuzzy logic based time variable damping TMD (fuzzy TMD) is compared to the baseline passive TMD as well as a conventional proportional-derivative (PD) controller. Forced vibration is introduced using a resonant harmonic sinusoidal excitation (i.e. same frequency as the fundamental frequency of the structure). Finally, the fuzzy TMD is compared to the baseline for the free vibration of a 15 story structure. For both structures studied, MATLAB based simulation results show that the passive TMD and the PD, both constant gain approaches, provide similar results whereas the fuzzy TMD yields half the settling time. This effort clearly demonstrates the potential of a variable gain (damping) strategy for the vibration suppression of buildings.
This paper describes a market-based solution to the problem of assigning mobile agents to tasks. The problem is formulated as the multiple depots, multiple traveling salesmen problem (MTSP), where agents and tasks operate in a market to achieve near-optimal solutions. We consider both the classical MTSP, in which the sum of all tour lengths is minimized, and the Min-Max MTSP, in which the longest tour is minimized. We compare the market-based solution with direct enumeration in small scenarios, and show that the results are nearly optimal. For the classical MTSP, we compare our results to linear programming, and show that the results are within 1 % of the best cost found by linear programming in more than 90 % of the runs, with a significant reduction in runtime. For the Min-Max case, we compare our method with Carlsson's algorithm and show an improvement of 5 % to 40 % in cost, albeit at an increase in runtime. Finally, we demonstrate the ability of the market-based solution to deal with changes in the scenario, e.g., agents leaving and entering the market. We show that the market paradigm is ideal for dealing with these changes during runtime, without the need to restart the algorithm, and that the solution reacts to the new scenarios in a quick and near-optimal way.
Wildfire is one of the most significant disturbances responsible for reshaping the terrain and changing the ecosystem of a particular region. Its detrimental effects on environment as well as human lives and properties, and growing trend in terms of frequency and intensity of wildfires over the last decade have necessitated the development of efficient forest fire management techniques. During the last three decades, Forest Fire Decision Support Systems (FFDSS) have been developed to help in the decision-making processes during forest fires by providing necessary information on fire detection, their status and behavior, and other aspects of forest fires. However, most of these decision support systems lack the capability of developing intelligent fire suppression strategies based upon current status and predicted behavior of forest fire. This paper presents an approach for development of efficient fireline building strategies via intelligent resource allocation. A Genetic Algorithm based approach has been proposed in this paper for resource allocation and optimum fireline building that minimizes the total damage due to wildland fires. The approach is based on a simulation–optimization technique in which the Genetic Algorithm uses advanced forest fire propagation models based upon Huygens principles for evaluation of cost index of its solutions. Both homogeneous and heterogeneous environmental conditions have been considered. Uncertainties in weather conditions as well as imperfect knowledge about exact vegetation and topographical conditions make exact prediction of wildfires very difficult. The paper incorporates Monte-Carlo simulations to develop robust strategies in uncertain conditions. Extensive simulations demonstrate the effectiveness of the proposed approach in efficient resource allocation for fighting
complex wildfires in uncertain and dynamic conditions.
UAV’s are being increasingly used today than ever before in both military and civil applications. A certain level of autonomy is imperative to the future of UAV’s. A quadrotor is a helicopter with four rotors, that make it more stable; but more complex to model and control. Characteristics that provide a clear advantage over other fixed wing UAV’s are VTOL and hovering capabilities as well as a greater maneuverability. Fuzzy logic control has been chosen over conventional control methods as it can deal effectively with highly nonlinear systems, allows for imprecise data and is extremely modular. The objective of this research endeavor is to present the steps of designing, building and simulating an intelligent flight control module for a quadrotor UAV. Validation of the math model developed is discussed using actual flight data. Excellent attitude tracking is demonstrated for near hover flight regimes. System design is comprehensively dealt with. The responses are analyzed and future work involving hardware-in-the-loop simulations is proposed.
Fuzzy logic is used in a variety of applications because of its universal approximator attribute and non-linear characteristics. But, it takes a lot of trial and error to come up with a set of membership functions and rule-base that will effectively work for a specific application. This process could be simplified by using a heuristic search algorithm like Genetic Algorithm (GA). In this paper, genetic fuzzy is applied to the task assignment for cooperating Unmanned Aerial Vehicles (UAVs) classified as the polygon visiting multiple traveling salesman problem (PVMTSP). The PVMTSP finds a lot of applications including UAV swarm routing. We propose a method of genetic fuzzy clustering that would be specific to PVMTSP problems and hence more efficient compared to k-means and c-means clustering. We developed two different algorithms using genetic fuzzy. One evaluates the distance covered by each UAV to cluster the search-space and the other uses a cost function that approximates the distance covered thus resulting in a reduced computational time. We compare these two approaches to each other as well as to an already benchmarked fuzzy clustering algorithm which is the current state-of-the-art. We also discuss how well our algorithm scales for increasing number of targets. The results are compared for small and large polygon sizes.
A genetic algorithm was used to optimize performance of a fuzzy inference system acting as a controller for a magnetically actuated CubeSat. A solely magnetically controlled satellite is a nonlinear, underactuated system for which the uncontrollable axis varies as a function of orbit position and attitude; variation is approximately periodic with orbit position. Therefore, controllability is not guaranteed, making solely magnetic control a less than ideal option for spacecraft requiring a high degree of pointing accuracy or spacecraft subject to relatively large disturbances. However, for small spacecraft, such as CubeSats, with modest pointing and disturbance rejection requirements, solely magnetic actuation is a good option. The genetic-algorithm-tuned fuzzy controller solution was compared to a similar linear quadratic regulator solution that was tuned to minimize the cost function used by the genetic algorithm. Both were optimized with respect to a single set of initial conditions. The genetic-algorithm-tuned fuzzy controller was found to be a lower-cost solution than the linear quadratic regulator for the optimized set of initial conditions. Additionally, a Monte Carlo analysis showed the genetic-algorithm-tuned fuzzy controller tended to settle faster than the linear quadratic regulator over a variety of initial conditions.
Proteomic analysis of biological samples in disease models or therapeutic intervention studies requires the ability to detect and identify biologically relevant proteins present in relatively low concentrations. The detection and analysis of these low-level proteins is hindered by the presence of a few proteins that are expressed in relatively high concentrations. In the case of muscle tissue, highly abundant structural proteins, such as actin, myosin, and tropomyosin, compromise the detection and analysis of more biologically relevant proteins. We have developed a practical protocol which exploits high-pH extraction to reduce or remove abundant structural proteins from skeletal muscle crude membrane preparations in a manner suitable for two dimensional gel electrophoresis. An initial whole-cell muscle lysate is generated by homogenization of powdered tissue in Tris-base. This lysate is subsequently partitioned into a supernatant and pellet containing the majority of structural proteins. Treatment of the pellet with high-pH conditions effectively releases structural proteins from membrane compartments which are then removed through ultracentrifugation. Mass spectrometric identification shows that the majority of protein spots reduced or removed by high-pH treatment were contractile proteins or contractile-related proteins. Removal of these proteins enabled successful detection and identification of minor proteins. Structural protein removal also results in significant improvement of gel quality and the ability to load higher amounts of total protein for the detection of lower abundant protein classes.
An extracellular phosphoglycan (exPG), present in the culturem edium of the promastigote form L oefi shmania donovani, was purified and structurally characterized. The purification scheme included ethanol precipitation of the culture medium, anion exchange chromatography, hydrophobic chromatography on phenyl-Sepharose, and preparative polyacrylamgeild e electrophoresis. Structural analysis by ‘H-’H NMR, methylation linkage analysis, and glycosidase digestion revealed that the exPG consisted of thfoel lowing structure: (CAP)+[P04-6Galp@1-4Manpal]lo-11-POr6GalpB1-4Man. The capw as found to be ones eovf eral small, neutral oligosaccharides, the most abundant of which was the trisaccharide Galp@l-4(Manpal-2)Man. The results indicated structural analogy to the cellular-derived lipophosphoglycan (LPG) from L. donovani. The important exceptions are a lacko f the lipid anchor, the entire phosphosaccharide core, and several of the repeating disaccharide units. Although the function of exPGis presently unknowni,t may play a protective role for the promastigote in the insect vector or during infection of a mammalian host
The primary structure of the major surface glycoconjugate of Leishmania donovani parasites, a lipophosphoglycan, has been further characterized. The repeating PO4-6Galp beta 1-4Man disaccharide units, which are a salient feature of the molecule, are shown to terminate with one of several neutral structures, the most abundant of which is the branched trisaccharide Galp beta 1-4(Manp alpha 1-2)Man. The phosphosaccharide core of lipophosphoglycan, which links the disaccharide repeats to a lipid anchor, contains 2 phosphate residues. One of the core phosphates has previously been localized on O-6 of the galactosyl residue distal to the lipid anchor; the second phosphate is now shown to be on O-6 of the mannosyl residue distal to the anchor and to bear an alpha-linked glucopyranosyl residue. Also, the anomeric configuration of the unusual 3-substituted Galf residue in the phosphosaccharide core is established as beta. The complete structure of the core is thus PO4-6Galp alpha 1-6Galp alpha 1-3Galf beta 1-3[Glcp alpha 1-PO4-6]Manp alpha 1-3Manp alpha 1-4GlcN alpha 1-. This further clarification of the structure of lipophosphoglycan may prove beneficial in determining the structure-function relationships of this highly unusual glycoconjugate.
Background: Role of apolipoprotein (apo) A-II on metabolism of high density lipoproteins (HDLs) is unknown.
Results: Conformational changes of apoA-I, the major apolipoprotein of HDL, caused by apoA-II in discoidal HDL are confined to two regions of apoA-I.
Conclusion: Interactions between the two major apolipoproteins in discoidal HDL are site specific.
Significance: Functional implications of HDL complexes will significantly benefit from such structural information.
Organovanadium compounds have been shown to be insulin sensitizers in vitro and in vivo. One potential biochemical mechanism for insulin sensitization by these compounds is that they inhibit protein tyrosine phosphatases (PTPs) that negatively regulate insulin receptor activation and signaling. In this study, bismaltolato oxovanadium (BMOV), a potent insulin sensitizer, was shown to be a reversible, competitive phosphatase inhibitor that inhibited phosphatase activity in cultured cells and enhanced insulin receptor activation in vivo. NMR and X-ray crystallographic studies of the interaction of BMOV with two different phosphatases, HCPTPA (human low molecular weight cytoplasmic protein tyrosine phosphatase) and PTP1B (protein tyrosine phosphatase 1B), demonstrated uncomplexed vanadium (VO ) in the active site. Taken together, these findings support phosphatase inhibition as a mechanism for insulin sensitization by BMOV 4 and other organovanadium compounds and strongly suggest that uncomplexed vanadium is the active component of these compounds.
Cardiolipin (CL) is a mitochondrial phospholipid essential for electron transport chain (ETC) integrity. CL-deficiency in humans is caused by mutations in the tafazzin (Taz) gene and results in a multisystem pediatric disorder, Barth syndrome (BTHS). It has been reported that tafazzin deficiency destabilizes mitochondrial respiratory chain complexes and affects supercomplex assembly. The aim of this study was to investigate the impact of Taz-knockdown on the mitochondrial proteomic landscape and metabolic processes, such as stability of respiratory chain supercomplexes and their interactions with fatty acid oxidation enzymes in cardiac muscle. Proteomic analysis demonstrated reduction of several polypeptides of the mitochondrial respiratory chain, including Rieske and cytochrome c1 subunits of complex III, NADH dehydrogenase alpha subunit 5 of complex I and the catalytic core-forming subunit of F0F1-ATP synthase. Taz gene knockdown resulted in upregulation of enzymes of folate and amino acid metabolic pathways in heart mitochondria, demonstrating that Tazdeficiency causes substantive metabolic remodeling in cardiac muscle. Mitochondrial respiratory chain supercomplexes are destabilized in CL-depleted mitochondria from Taz knockdown hearts resulting in disruption of the interactions between ETC and the fatty acid oxidation enzymes, very long-chain acyl-CoA dehydrogenase and long-chain 3-hydroxyacylCoA dehydrogenase, potentially affecting the metabolic channeling of reducing equivalents between these two metabolic pathways. Mitochondria-bound myoglobin was significantly reduced in Taz-knockdown hearts, potentially disrupting intracellular oxygen delivery to the oxidative phosphorylation system. Our results identify the critical pathways affected by the Taz-deficiency in mitochondria and establish a future framework for development of therapeutic options for BTHS.
Cardiac myosin binding protein-C (cMyBP-C) is a thick filament assembly protein that stabilizes sarcomeric structure and regulates cardiac function; however, the profile of cMyBP-C degradation after myocardial infarction (MI) is unknown. We hypothesized that cMyBP-C is sensitive to proteolysis and is specifically increased in the bloodstream post-MI in rats and humans. Under these circumstances, elevated levels of degraded cMyBP-C could be used as a diagnostic tool to confirm MI. To test this hypothesis, we first established that cMyBP-C dephosphorylation is directly associated with increased degradation of this myofilament protein, leading to its release in vitro. Using neonatal rat ventricular cardiomyocytes in vitro, we were able to correlate the induction of hypoxic stress with increased cMyBP-C dephosphorylation, degradation, and the specific release of N′-fragments. Next, to define the proteolytic pattern of cMyBP-C post-MI, the left anterior descending coronary artery was ligated in adult male rats. Degradation of cMyBP-C was confirmed by a reduction in total cMyBP-C and the presence of degradation products in the infarct tissue. Phosphorylation levels of cMyBP-C were greatly reduced in ischemic areas of the MI heart compared to non-ischemic regions and sham control hearts. Post-MI plasma samples from these rats, as well as humans, were assayed for cMyBP-C and its fragments by sandwich ELISA and immunoprecipitation analyses. Results showed significantly elevated levels of cMyBP-C in the plasma of all post-MI samples. Overall, this study suggests that cMyBP-C is an easily releasable myofilament protein that is dephosphorylated, degraded and released into the circulation post-MI. The presence of elevated levels of cMyBP-C in the blood provides a promising novel biomarker able to accurately rule in MI, thus aiding in the further assessment of ischemic heart disease.
We have designed ROS-activated cytotoxic agents that are active against AML cancer cells. In this study the mechanism and synergistic effects against cells co-expressing the AML oncogenes MLL-AF9 fusion and FLT3-ITD was investigated. The agent had an IC50 value of 1.8±0.3 μM with a selectivity of 9-fold compared to untransformed cells. Treatment induced DNA strand breaks, apoptosis, and cell cycle arrest. Proteomics and transcriptomics revealed enhanced expression of the pentose phosphate pathway, DNA repair, and pathways common to cell stress. Western blotting confirmed repair by homologous recombination. Importantly, RAC1 treatment was synergistic in combination with multiple pathway targeting therapies in AML cells but less so in untransformed cells. Taken together, these results demonstrate that RAC1 can selectively target poor prognosis AML and do so by creating DNA double strand breaks that require homologous recombination.
Bacterial methionine aminopeptidase (MAP) is a protease that removes methionine from the N termini of newly synthesized bacterial proteins after the peptide deformylase enzyme cleaves the formyl group from the initiator formylmethionine. MAP is an essential bacterial gene product and thus represents a potential target for therapeutic intervention. A fundamental challenge in the antibacterial drug discovery field is demonstrating conclusively that compounds with in vitro enzyme inhibition activity produce the desired antibacterial effect by interfering with the same target in whole bacterial cells. One way to address the activity of inhibitor compounds is by profiling cellular biomarkers in whole bacterial cells using compounds that are known inhibitors of a particular target. However, in the case of MAP, no specific inhibitors were available for such studies. Instead, a genetically attenuated MAP strain was generated in which MAP expression was placed under the control of an inducible arabinose promoter. Thus, MAP inhibition in whole cells could be mimicked by growth in the absence of arabinose. This genetically attenuated strain was used as a benchmark for MAP inhibition by profiling whole-cell lysates for unprocessed proteins using surface-enhanced laser desorption ionization–time of flight mass spectrometry (MS). Eight proteins between 4 and 14 kDa were confirmed as being unprocessed and containing the initiator methionine by adding back purified MAP to the preparations prior to MS analysis. Upon establishing these unprocessed proteins as biomarkers for MAP inhibition, the assay was used to screen small-molecule chemical inhibitors of purified MAP for whole-cell activity. Fifteen compound classes yielded three classes of compound with whole-cell activity for further optimization by chemical expansion. This report presents the development, validation, and implementation of a whole-cell inhibition assay for MAP.
Commonly used methods for isolated enzyme inhibitor screening typically rely on fluorescent or chemiluminescent detection techniques that are often indirect and/or coupled assays. Mass spectrometry (MS) has been widely reported for measuring the conversion of substrates to products for enzyme assays and has more recently been demonstrated as an alternative readout system for inhibitor screening. In this report, a high-throughput mass spectrometry (HTMS) readout platform, based on the direct measurement of substrate conversion to product, is presented. The rapid ionization and desorption features of a new generation matrix-assisted laser desorption ionization-triple quadrupole (MALDI-QqQ) mass spectrometer are shown to improve the speed of analysis to greater than 1 sample per second while maintaining excellent Z′ values. Furthermore, the readout was validated by demonstrating the ability to measure IC50 values for several known kinase inhibitors against cyclic AMP–dependent protein kinase (PKA). Finally, when the assay performance was compared with a common ADPaccumulation readout system, this HTMS approach produced better signal-to-background ratios, higher Z′ values, and a reagent cost of about $0.03 per well compared with about $0.60 per well for the fluorescence assay. Collectively, these data demonstrate that a MALDI-QqQ-MS–based readout platform offers significant advantages over the commonly used assays in terms of speed, sensitivity, reproducibility, and reagent cost. (Journal of Biomolecular Screening 2008:1007-1013)
Candida albicans is a leading pathogen in infections of central venous catheters, which are frequently infused with heparin. Binding of C. albicans to medically relevant concentrations of soluble and plate-bound heparin was demonstrable by confocal microscopy and enzyme-linked immunosorbent assay (ELISA). A sequencebased search identified 34 C. albicans surface proteins containing ≥1 match to linear heparin-binding motifs. The virulence factor Int1 contained the most putative heparin-binding motifs (n = 5); peptides encompassing 2 of 5 motifs bound to heparin-Sepharose. Alanine substitution of lysine residues K805/K806 in 804QKKHQIHK811 (motif 1 of Int1) markedly attenuated biofilm formation in central venous catheters in rats, whereas alanine substitution of K1595/R1596 in 1593FKKRFFKL1600 (motif 4 of Int1) did not impair biofilm formation. Affinity-purified immunoglobulin G (IgG) recognizing motif 1 abolished biofilm formation in central venous catheters; preimmune IgG had no effect. After heparin treatment of C. albicans, soluble peptides from multiple C. albicans surface proteins were detected, such as Eno1, Pgk1, Tdh3, and Ssa1/2 but not Int1, suggesting that heparin changes candidal surface structures and may modify some antigens critical for immune recognition. These studies define a new mechanism of biofilm formation for C. albicans and a novel strategy for inhibiting catheter-associated biofilms.